Serotonin- and Dopamine-Related Gene Expression in db/db Mice Islets and in MIN6 ß-Cells Treated with Palmitate and Oleate.

High circulating nonesterified fatty acids (NEFAs) concentration, often reported in diabetes, leads to impaired glucose-stimulated insulin secretion (GSIS) through not yet well-defined mechanisms. Serotonin and dopamine might contribute to NEFA-dependent ß-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated ß-cells may enhance the expression of the serotonin receptor Htr2c, affecting insulin secretion. Additionally, the expression of monoamine-oxidase type B (Maob) seems to be lower in islets from humans and mice with diabetes compared to nondiabetic islets, which may lead to increased monoamine concentrations. We assessed the expression of serotonin- and dopamine-related genes in islets from db/db and wild-type (WT) mice. In addition, the effect of palmitate and oleate on the expression of such genes, 5HT content, and GSIS in MIN6 ß-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 ß-cells in response to palmitate and oleate treatment compared to vehicle. Reduced 5HT content and impaired GSIS in response to palmitate (-25%; p < 0.0001) and oleate (-43%; p < 0.0001) were detected in MIN6 ß-cells. In conclusion, known defects of GSIS in islets from db/db mice and MIN6 ß-cells treated with NEFAs are accompanied by reduced Maob expression and reduced 5HT content.

Development and assessment of the disposition index based on the oral glucose tolerance test in subjects with different glycaemic status.

Insulin secretion and insulin sensitivity indexes are related by hyperbolic functions, allowing the calculation of the disposition index (DI) as the product of the acute insulin response (AIR) and the insulin sensitivity index (Si) from intravenous glucose tolerance test (IVGTT). Our objective was to develop an oral-DI based on the oral glucose tolerance test (OGTT) and to assess its association with glucose tolerance status. This research is structured in three studies. Study 1: OGTT were performed in 833 non-diabetic Chilean women (18-60 years) without family history of diabetes mellitus. Study 2: an independent group of n = 57 non-diabetic (18-46 years) without family history of diabetes mellitus carried out an OGTT and an abbreviated IVGTT. Study 3: a sample of 1674 Chilean adults (18-60 years) with different glycaemic status performed an OGTT. An adequate statistical fit for a rectangular hyperbola was found between the area under the curve of insulin-to-glucose ratio (AUCI/G-R) and the Matsuda ISI-COMP index (study 1). The oral-DI derived as AUCI/G-R × ISI-COMP was previously termed insulin-secretion-sensitivity index-2 (ISSI-2). ISSI-2 significantly correlated with DI from IVGTT (rho = 0.34; p = 0.009) (study 2). ISSI-2 shows important differences across groups of subjects with different glycaemic status (study 3). We have confirmed that ISSI-2 replicates the mathematical properties of DI, showing significant correlations with DI from the abbreviated MM-IVGTT. These results indicate that ISSI-2 constitutes a surrogate measure of insulin secretion relative to insulin sensitivity and emphasizes the pivotal role of impaired insulin secretion in the development of glucose homeostasis dysregulation.

Plasma levels of interleukin-6 and interleukin-18 after an acute physical exercise: relation with post-exercise energy intake in twins.

Increased interleukin-6 (IL-6) plasma levels have been described to occur during physical exercise. A relative reduction in energy intake after physical activity has also been reported after exercise, indicating a possible involvement of IL-6 as an anorexigenic factor. Given the possible effect of interleukins on appetite, we assessed whether a controlled physical activity bout is related with changes in IL-6, IL-6 soluble receptor (IL-6sR), gp130 and interleukin-18 (IL-18) plasma levels, as well as their relation with post-exercise energy intake. A co-twin intervention study was carried out with five young male monozygotic twin pairs. One co-twin performed 45 min of submaximal exercise on a treadmill near the anaerobic threshold ending with 7 min at 90 % VO(2) max, while his co-twin remained non-active. Ad libitum energy intake was tested through a carbohydrate-rich meal test. Venous blood samples were drawn at baseline, immediately after exercise and after the meal ingestion. Plasma concentrations of IL-6, IL-6sR, gp130 and IL-18 were measured via ELISA. IL-6 plasma levels increased after physical activity bout (2.6-fold change; p = 0.04). A less marked trend, although still significant, was observed for plasma levels of IL-6sR and gp130. Plasma levels of IL-18 did not significantly change during exercise. The twins who exercised exhibited significantly lower energy intake (181 versus 1,195 kcal; p = 0.04), compared to the co-twins who remained resting. The present study in monozygotic twins shows increased IL-6 plasma levels after acute physical exercise with a significant reduction in energy intake, supporting a linkage between IL-6 and acute post-exercise eating behaviour.

Copy number polymorphism of the salivary amylase gene: implications in human nutrition research.

The salivary α-amylase is a calcium-binding enzyme that initiates starch digestion in the oral cavity. The α-amylase genes are located in a cluster on the chromosome that includes salivary amylase genes (AMY1), two pancreatic α-amylase genes (AMY2A and AMY2B) and a related pseudogene. The AMY1 genes show extensive copy number variation which is directly proportional to the salivary α-amylase content in saliva. The α-amylase amount in saliva is also influenced by other factors, such as hydration status, psychosocial stress level, and short-term dietary habits. It has been shown that the average copy number of AMY1 gene is higher in populations that evolved under high-starch diets versus low-starch diets, reflecting an intense positive selection imposed by diet on amylase copy number during evolution. In this context, a number of different aspects can be considered in evaluating the possible impact of copy number variation of the AMY1 gene on nutrition research, such as issues related to human diet gene evolution, action on starch digestion, effect on glycemic response after starch consumption, modulation of the action of α-amylases inhibitors, effect on taste perception and satiety, influence on psychosocial stress and relation to oral health.